Correlação de Spearman = 0,087
38 FIGURA 1
Angiografia confirmando ORVCR na arcada temporal inferior afetando área macular com sofrimento vascular.
39 FIGURA 2
Angiografia com boa reabsorção da hemorragias retiniana, com boa perfusão capilar, sem sinais de extravasamento vascular ou neovasos.
40 5.0 DISCUSSÃO
A oclusão de ramo da veia central da retina (ORVCR) é um grave problema vascular que afeta a acuidade visual do paciente principalmente devido ao edema macular que se forma por sua consequência. Atualmente, todos os tratamentos têm como principal objetivo reduzir esse edema.
O primeiro tratamento aceito constituía na fotocoagulação a laser em padrão, que foi demonstrado no estudo Branch Retinal Vein Oclusion Study (BVOS, 1984). Outros estudos recomendavam o uso de laser em grid (LANG, 1993; ESRICK, 2005). Foram avaliados (LANG, 1993) a eficácia e segurança no uso de laser de argônio no tratamento de neovascularização pre-retiniana e/ou na persistência de edema macular por mais de 3 meses com após a oclusão com AV ≤ 20/40 e encontraram uma melhora estatisticamente significativa na comparação de olhos tratados com olho não tratados. Outros estudos (ESRICK, 2005), recomendaram o uso de múltiplas sessões de laser. Apesar dos estudos, a maioria dos pacientes experimentava uma melhora limitada da AV após o tratamento.
Apesar do ganho limitado de acuidade visual (HAYREH, 1993), mesmo com redução do edema macular, os pacientes apresentavam boa estabilidade em longo prazo, impedindo complicações futuras como neovascularização descontrolada e hemorragia vítrea (BVOS, 1994; LANG, 1993). Apesar desses benefícios, era preciso ter uma boa visualização da retina no momento do laser (ESRICK, 2005) o que na maioria dos casos significa aguardar vários dias e até meses para isso aumentando o número de visitas ao médico e o custo.
A triancinolona acetonida, apesar de apresentar bons resultados (CHEN, 2006; OZKIRIS, 2006; AVITABILE, 2005; CEKIC, 2005), também apresentou uma variedade de efeitos colaterais como o aumento na indução de catarata e a hipertensão intraocular, além de ter resultados com duração limitada (CEKIC, 2005).
A descoberta do VEGF (SENGER, 1983) e seu efeito mitótico sobre as células do endotélio vascular (SENGER, 1990) abriram novas linhas de estudos e de tratamentos com possibilidades até então desconhecidas. Sua produção é feita por macrófagos, linfócitos T, células tumorais e, no olho, pelas células do EPR, e o aumento
41 na sua produção ocorre principalmente em condições de hipóxia, que é o principal indutor da produção de VEGF (SHIMA, 1995).
Tanto na embriogênese da retina quanto nas retinopatias proliferativas, a expressão de VEGF está temporal, espacial e quantitativamente relacionada com a formação de neovasos (Miller, 1994).
Os estudos em animais mostram que a expressão aumentada de VEGF é uma condição necessária para a indução da neovascularização ocular, e que somente esse aumento é suficiente para induzir esse processo (AIELLO, 1997; VINORES, 1997; SENGER, 1983; ANTONETTI 1999). O aumento da expressão de VEGF no EPR e nos fotorreceptores de ratos promove aumento da permeabilidade vascular, aumento da adesão leucocitária e formação de neovasos de coroide (SPILSBURY, 2000). Em macacos, a injeção intravítrea de VEGF provoca o aparecimento de neovasos retinianos cujas características histológicas e funcionais são muito semelhantes aos encontrados nas retinopatias proliferativas (TOLENTINO, 1996, 2002). Por outro lado, a injeção intravítrea de anticorpo anti-VEGF previne a formação de neovasos sub-retinianos (ISHIDA, 2003).
Todos esses resultados mostram a importância do VEGF no processo de angiogênese, e abriram caminho para as novas terapias antiangiogênicas de retinopatias proliferativas.
A partir desses estudos, em teoria, a inibição do VEGF poderia ser uma vantagem terapêutica em casos de retinopatia vasoproliferativas. Estudos recentes (MELVIN, 2006) comprovaram a eficácia dessa teoria, mas com uma duração media dos efeitos do bevacizumabe intraocular entorno de 2,1 meses. Um estudo multicêntrico prospectivo (BRAVO, 2010) avaliou o uso de múltiplas aplicações de inibidor de VEGF intravítreo em pacientes com ORVCR na tentativa de obter resultados mais estáveis em longo prazo.
O bevacizumabe intravítreo vem apresentando bons resultados em relação a melhora da acuidade visual em pacientes com ORVCR sem os efeitos colaterais de outros tratamentos, com uma boa biossegurança sem sinais de toxicidade ocular.
42 O uso do bevacizumabe intravítreo no tratamento de ORVCR oferece uma vantagem significativa na rápida redução do edema macular, recuperando a AV e favorecendo a reabsorção da hemorragia. Esse fator acelera a visualização da retina possibilitando a fotocoagulação a laser.
Efeitos sistêmicos adversos com o uso de bevacizumabe intravítreo ainda não foram comprovados apesar de teoricamente possíveis, o que favorece o uso do laser e a redução no numero de aplicações.
Baseado nesses estudos e em nossa experiência, tentamos combinar o que havia de melhor entre os tratamentos atuais combinando uma única aplicação intraocular de inibidor de VEGF, o bevacizumabe, com dose de 1,25mg/0,05ml, logo após o diagnóstico, seguido de fotocoagulação a laser entre 30 e 45 dias após a aplicação. Um tratamento relativamente simples, de baixo custo, que pode ser realizado com poucas visitas ao médico, gerando uma melhora da AV com estabilidade a longo prazo para o paciente. Com isso, alcançamos um ganho médio de 0.42 LogMAR.
43 6.0 CONCLUSÃO
Esse estudo de curto prazo com 26 pacientes sugere que o uso combinado de bevacizumabe intravítreo seguido de fotocoagulação a laser na área afetada pode representar uma boa opção de tratamento para ORVCR com melhora da acuidade visual e estabilidade dos resultados. Adicionalmente, vale ressaltar que esses benefícios foram obtidos com menor numero de visitas ao médico e com custo reduzido em comparação a outros novos tratamentos propostos. Os resultados obtidos comprovam a necessidade de novos estudos multicêntricos com caso controle para uma maior compreensão sobre o tema.
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